# Deciphering the Molecular Assembly Mechanism of Giant DNA Viruses

> **NIH NIH R01** · UNIVERSITY OF TEXAS EL PASO · 2020 · $344,458

## Abstract

Project Summary/Abstract
Over the last two decades, many giant DNA viruses have been discovered, some of which are bigger than a
small cell. How these giant viruses assemble their virion shell from thousands of simple protein building blocks
so precisely is a mystery. However, the sheer size of these viruses poses a significant challenge to currently
available techniques. This project will tackle this challenge by using a marine giant virus Cafeteria
roenbergensis virus (CroV) as a model to decipher the assembly mechanism of giant viruses, and as an
opportunity to develop technology to push the resolution limit of these gigantic structures to the atomic level.
During the last five years, cryo-electron microscopy (cryo-EM) has become an increasingly powerful tool to
study the structures of biological molecules at atomic resolution, earning its developers the 2017 Nobel Prize in
Chemistry. We will collect higher quality images using state-of-the-art cryo-EM equipped with latest new
hardware, such as energy filters, direct electron detectors and phase plates. Using these images together with
new software algorithms, we will determine the structure of giant CroV to high resolution by image analyses
and reconstruction. Structures of individual CroV proteins will also be solved to atomic resolution by cryo-EM
using various methods and docked into the cryo-EM reconstructed maps. The resultant pseudo-atomic
structure will allow characterization of the ultrastructural features and architecture of CroV, building the
essential foundation to unravel the assembly of giant viruses. The structure information will be combined with
classic biophysical, molecular dynamic simulation, mathematical modeling, and computational analyses to
evaluate the novel assembly model of giant viruses. In the new assembly model, the protein shells of giant
viruses are assembled continuously from the 5-fold vertices in an interesting spiral way instead of assembled
from patches in a step-wise fashion previously assumed. Giant virus protein shell is assembled from protein
building block similar to other viruses, including many human pathogens. Some giant viruses have been
associated with human diseases such as pneumonia and cognitive functional change. Understanding these
principles governing the assembly of giant viruses will improve the development of therapeutic agents to inhibit
virus assembly, thus providing a new avenue for preventing and treating viral diseases in general. Elucidation
of the molecular interactions that drive assembly of these giant viruses will also shed light on how to control
protein-protein interactions effectively, facilitating the rational design of virus-like nanoparticles with a wide size
range for biomedical and other nano-applications. Since some giant viruses are bigger than a small cell,
techniques and methods developed in this project will push the limits of structural biology and provide new and
useful tools to study even larger supramolecular as...

## Key facts

- **NIH application ID:** 9936316
- **Project number:** 5R01GM129525-02
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Chuan Xiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,458
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9936316

## Citation

> US National Institutes of Health, RePORTER application 9936316, Deciphering the Molecular Assembly Mechanism of Giant DNA Viruses (5R01GM129525-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9936316. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*